Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.
Identifieur interne : 000392 ( Hal/Corpus ); précédent : 000391; suivant : 000393Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.
Auteurs : Benjamin F J. Verhaaren ; Stéphanie Debette ; Joshua C. Bis ; Jennifer A. Smith ; M Kamran Ikram ; Hieab H. Adams ; Ashley H. Beecham ; Kumar B. Rajan ; Lorna M. Lopez ; Sandra Barral ; Mark A. Van Buchem ; Jeroen Van Der Grond ; Albert V. Smith ; Katrin Hegenscheid ; Neelum T. Aggarwal ; Mariza De Andrade ; Elizabeth J. Atkinson ; Marian Beekman ; Alexa S. Beiser ; Susan H. Blanton ; Eric Boerwinkle ; Adam M. Brickman ; R Nick Bryan ; Ganesh Chauhan ; Christopher P L H. Chen ; Vincent Chouraki ; Anton J M. De Craen ; Fabrice Crivello ; Ian J. Deary ; Joris Deelen ; Philip L. De Jager ; Carole Dufouil ; Mitchell S V. Elkind ; Denis A. Evans ; Paul Freudenberger ; Rebecca F. Gottesman ; Vilmundur Gu Nason ; Mohamad Habes ; Susan R. Heckbert ; Gerardo Heiss ; Saima Hilal ; Edith Hofer ; Albert Hofman ; Carla A. Ibrahim-Verbaas ; David S. Knopman ; Cora E. Lewis ; Jiemin Liao ; David C M. Liewald ; Michelle Luciano ; Aad Van Der Lugt ; Oliver O. Martinez ; Richard Mayeux ; Bernard Mazoyer ; Mike Nalls ; Matthias Nauck ; Wiro J. Niessen ; Ben A. Oostra ; Bruce M. Psaty ; Kenneth M. Rice ; Jerome I. Rotter ; Bettina Von Sarnowski ; Helena Schmidt ; Pamela J. Schreiner ; Maaike Schuur ; Stephen S. Sidney ; Sigurdur Sigurdsson ; P Eline Slagboom ; David J M. Stott ; John C. Van Swieten ; Alexander Teumer ; Anna Maria Töglhofer ; Matthew Traylor ; Stella Trompet ; Stephen T. Turner ; Christophe Tzourio ; Hae-Won Uh ; André G. Uitterlinden ; Meike W. Vernooij ; Jing J. Wang ; Tien Y. Wong ; Joanna M. Wardlaw ; B Gwen Windham ; Katharina Wittfeld ; Christiane Wolf ; Clinton B. Wright ; Qiong Yang ; Wei Zhao ; Alex Zijdenbos ; J Wouter Jukema ; Ralph L. Sacco ; Sharon L R. Kardia ; Philippe Amouyel ; Thomas H. Mosley ; W T Longstreth ; Charles C. Decarli ; Cornelia M. Van Duijn ; Reinhold Schmidt ; Lenore J. Launer ; Hans J. Grabe ; Sudha S. Seshadri ; M Arfan Ikram ; Myriam FornageSource :
- Circulation: Cardiovascular Genetics [ 1942-325X ] ; 2015-03-31.
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Abstract
The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
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DOI: 10.1161/CIRCGENETICS.114.000858
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Hal:hal-01198723Le document en format XML
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Grabe</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-268175" status="INCOMING"> <orgName>Department of Psychiatry and Psychotherapy</orgName> <desc> <address> <addrLine>Rostocker Chaussee 70- 18435 Stralsund</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-380134" type="direct"></relation> <relation active="#struct-380135" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-380134" type="direct"><org type="institution" xml:id="struct-380134" status="INCOMING"> <orgName>University Medicine Greifswald,</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-380135" type="direct"><org type="institution" xml:id="struct-380135" status="INCOMING"> <orgName>HELIOS Hospital Stralsund</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Seshadri, Sudha S" sort="Seshadri, Sudha S" uniqKey="Seshadri S" first="Sudha S" last="Seshadri">Sudha S. Seshadri</name><affiliation><hal:affiliation type="institution" xml:id="struct-423110" status="INCOMING"> <orgName>Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><hal:affiliation type="institution" xml:id="struct-420494" status="INCOMING"> <orgName>Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><hal:affiliation type="institution" xml:id="struct-420496" status="INCOMING"> <orgName>Brown Foundation Institute of Molecular Medicine, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA.</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:hal-01198723</idno><idno type="halId">hal-01198723</idno><idno type="halUri">https://hal.archives-ouvertes.fr/hal-01198723</idno><idno type="url">https://hal.archives-ouvertes.fr/hal-01198723</idno><idno type="doi">10.1161/CIRCGENETICS.114.000858</idno><date when="2015-03-31">2015-03-31</date><idno type="wicri:Area/Hal/Corpus">000392</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.</title><author><name sortKey="Verhaaren, Benjamin F J" sort="Verhaaren, Benjamin F J" uniqKey="Verhaaren B" first="Benjamin F J" last="Verhaaren">Benjamin F J. Verhaaren</name><affiliation><hal:affiliation type="institution" xml:id="struct-420509" status="INCOMING"> <orgName>Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stéphanie" last="Debette">Stéphanie Debette</name><affiliation><hal:affiliation type="institution" xml:id="struct-431520" status="INCOMING"> <orgName>INSERM U897, University of Bordeaux, France</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name><affiliation><hal:affiliation type="institution" xml:id="struct-420488" status="INCOMING"> <orgName>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A" last="Smith">Jennifer A. 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Adams</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-21646" status="OLD"> <orgName>Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique</orgName> <desc> <address> <addrLine>Boulevard Sébastien Brandt BP 10413 67412 ILLKIRCH CEDEX</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-300320" type="direct"></relation> <relation name="UMR7175" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-300320" type="direct"><org type="institution" xml:id="struct-300320" status="VALID"> <orgName>Université Louis Pasteur - Strasbourg I</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle name="UMR7175" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Beecham, Ashley H" sort="Beecham, Ashley H" uniqKey="Beecham A" first="Ashley H" last="Beecham">Ashley H. 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UMR 5296</orgName> <desc> <address> <addrLine>Université de Bordeaux PAC Carreire, case 71 UMR 5296, GIN, CNRS, CEA, Univ. de Bordeaux 146 rue Léo-Saignat, CS 61292 33076 Bordeaux Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.gin.cnrs.fr/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="DSV/I2BM" active="#struct-300016" type="direct"></relation> <relation name="UMR5296" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"><orgName>Université de Bordeaux</orgName><orgName type="acronym">UB</orgName><desc><address><addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine><country key="FR"></country></address><ref type="url">http://www.u-bordeaux.fr/</ref></desc></org></tutelle><tutelle name="DSV/I2BM" active="#struct-300016" type="direct"><org type="institution" xml:id="struct-300016" status="VALID"> <orgName>Commissariat à l'énergie atomique et aux énergies alternatives</orgName> <orgName type="acronym">CEA</orgName> <desc> <address> <addrLine>Centre de SaclayCentre de GrenobleCentre de Cadaracheetc</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.cea.fr/</ref> </desc> </org></tutelle><tutelle name="UMR5296" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Nalls, Mike" sort="Nalls, Mike" uniqKey="Nalls M" first="Mike" last="Nalls">Mike Nalls</name><affiliation><hal:affiliation type="institution" xml:id="struct-420532" status="INCOMING"> <orgName>Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Nauck, Matthias" sort="Nauck, Matthias" uniqKey="Nauck M" first="Matthias" last="Nauck">Matthias Nauck</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-167197" status="INCOMING"> <orgName>Institute of Clinical Chemistry and Laboratory Medicine</orgName> <desc> <address> <addrLine>D-17475 Greifswald</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-462070" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-462070" type="direct"><org type="institution" xml:id="struct-462070" status="VALID"> <orgName>University of Greifswald</orgName> <desc> <address> <addrLine>Ernst-Moritz-Arndt- University of Greifswald Domstraße 11 17489 Greifswald</addrLine> <country key="DE"></country> </address> <ref type="url">https://www.uni-greifswald.de/en/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J" last="Niessen">Wiro J. 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Wardlaw</name><affiliation><hal:affiliation type="institution" xml:id="struct-61277" status="VALID"> <orgName>University of Edinburgh</orgName> <desc> <address> <addrLine>Old College South Bridge Edinburgh EH8 9YL</addrLine> <country key="GB"></country> </address> <ref type="url">http://www.ed.ac.uk/home</ref> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Windham, B Gwen" sort="Windham, B Gwen" uniqKey="Windham B" first="B Gwen" last="Windham">B Gwen Windham</name><affiliation><hal:affiliation type="institution" xml:id="struct-432667" status="INCOMING"> <orgName>Division of geriatrics, gerontology</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Wittfeld, Katharina" sort="Wittfeld, Katharina" uniqKey="Wittfeld K" first="Katharina" last="Wittfeld">Katharina Wittfeld</name><affiliation><hal:affiliation type="institution" xml:id="struct-431764" status="INCOMING"> <orgName>Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany </orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Wolf, Christiane" sort="Wolf, Christiane" uniqKey="Wolf C" first="Christiane" last="Wolf">Christiane Wolf</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-430328" status="INCOMING"> <orgName>Ninewells Hospital and Medical School, Biomedical Research Centre</orgName> <desc> <address> <country key="GB"></country> </address> </desc> <listRelation> <relation active="#struct-300845" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-300845" type="direct"><org type="institution" xml:id="struct-300845" status="VALID"> <orgName>University of Dundee</orgName> <date type="start">2017-02-16</date> <desc> <address> <addrLine>University of DundeeNethergateDundeeScotland, UKDD1 4HN </addrLine> <country key="GB"></country> </address> <ref type="url">https://www.dundee.ac.uk/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Wright, Clinton B" sort="Wright, Clinton B" uniqKey="Wright C" first="Clinton B" last="Wright">Clinton B. Wright</name><affiliation><hal:affiliation type="department" xml:id="struct-97362" status="VALID"> <orgName>Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor]</orgName> <orgName type="acronym">AOSS</orgName> <desc> <address> <addrLine>Ann Arbor, MI 48109</addrLine> <country key="US"></country> </address> <ref type="url">http://clasp.engin.umich.edu</ref> </desc> <listRelation> <relation active="#struct-24332" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-24332" type="direct"><org type="institution" xml:id="struct-24332" status="VALID"> <orgName>University of Michigan [Ann Arbor]</orgName> <desc> <address> <addrLine>500 Church Street Ann Arbor, MI 48109-1090</addrLine> <country key="US"></country> </address> <ref type="url">http://www.umich.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><hal:affiliation type="institution" xml:id="struct-430101" status="INCOMING"> <orgName>Department of Mechanical and Aerospace Engineering, University of Miami</orgName> <desc> <address> <addrLine>1251 Memorial Drive, Suite EB205, Coral Gables, FL 33146</addrLine> <country key="US"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-182245" status="VALID"> <idno type="IdRef">150044909</idno> <idno type="RNSR">200017461J</idno> <orgName>Centre d'Immunologie de Marseille - Luminy</orgName> <orgName type="acronym">CIML</orgName> <date type="start">2012</date> <desc> <address> <addrLine>Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation name="UMR_S 1104" active="#struct-303623" type="direct"></relation> <relation name="UM 2" active="#struct-198056" type="direct"></relation> <relation name="UMR7280" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle name="UMR_S 1104" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle name="UM 2" active="#struct-198056" type="direct"><org type="institution" xml:id="struct-198056" status="VALID"> <idno type="IdRef">15863621X</idno> <idno type="ISNI">0000 0001 2176 4817</idno> <orgName>Aix Marseille Université</orgName> <orgName type="acronym">AMU</orgName> <date type="start">2012-01-01</date> <desc> <address> <addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-amu.fr/</ref> </desc> </org></tutelle><tutelle name="UMR7280" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Zijdenbos, Alex" sort="Zijdenbos, Alex" uniqKey="Zijdenbos A" first="Alex" last="Zijdenbos">Alex Zijdenbos</name><affiliation><hal:affiliation type="institution" xml:id="struct-420514" status="INCOMING"> <orgName>Biospective, Inc., Montreal, Quebec, Canada</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J Wouter" last="Jukema">J Wouter Jukema</name><affiliation><hal:affiliation type="institution" xml:id="struct-307012" status="INCOMING"> <orgName>Interuniversity Cardiology Institute Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Sacco, Ralph L" sort="Sacco, Ralph L" uniqKey="Sacco R" first="Ralph L" last="Sacco">Ralph L. Sacco</name><affiliation><hal:affiliation type="institution" xml:id="struct-432668" status="INCOMING"> <orgName>Dept of Epidemiology & Public Health Sciences</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L R" last="Kardia">Sharon L R. Kardia</name><affiliation><hal:affiliation type="institution" xml:id="struct-432651" status="INCOMING"> <orgName>Dept of Epidemiology, School of Public Health, Univ of Michigan, Ann Arbor, MI</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><hal:affiliation type="institution" xml:id="struct-423244" status="INCOMING"> <orgName>Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H" last="Mosley">Thomas H. Mosley</name><affiliation><hal:affiliation type="institution" xml:id="struct-420520" status="INCOMING"> <orgName>Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Longstreth, W T" sort="Longstreth, W T" uniqKey="Longstreth W" first="W T" last="Longstreth">W T Longstreth</name><affiliation><hal:affiliation type="institution" xml:id="struct-420543" status="INCOMING"> <orgName>Department of Neurology, University of Washington, Seattle, Washington, USA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Decarli, Charles C" sort="Decarli, Charles C" uniqKey="Decarli C" first="Charles C" last="Decarli">Charles C. Decarli</name><affiliation><hal:affiliation type="institution" xml:id="struct-423113" status="INCOMING"> <orgName>Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><hal:affiliation type="institution" xml:id="struct-420505" status="INCOMING"> <orgName>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name><affiliation><hal:affiliation type="institution" xml:id="struct-196396" status="VALID"> <orgName>Austrian Institute of Technology [Vienna]</orgName> <orgName type="acronym">AIT</orgName> <desc> <address> <addrLine>Donau-City-Straße 11220 Vienna</addrLine> <country key="AT"></country> </address> <ref type="url">http://www.ait.ac.at/</ref> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><hal:affiliation type="institution" xml:id="struct-420531" status="INCOMING"> <orgName>Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Grabe, Hans J" sort="Grabe, Hans J" uniqKey="Grabe H" first="Hans J" last="Grabe">Hans J. Grabe</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-268175" status="INCOMING"> <orgName>Department of Psychiatry and Psychotherapy</orgName> <desc> <address> <addrLine>Rostocker Chaussee 70- 18435 Stralsund</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-380134" type="direct"></relation> <relation active="#struct-380135" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-380134" type="direct"><org type="institution" xml:id="struct-380134" status="INCOMING"> <orgName>University Medicine Greifswald,</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-380135" type="direct"><org type="institution" xml:id="struct-380135" status="INCOMING"> <orgName>HELIOS Hospital Stralsund</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Seshadri, Sudha S" sort="Seshadri, Sudha S" uniqKey="Seshadri S" first="Sudha S" last="Seshadri">Sudha S. Seshadri</name><affiliation><hal:affiliation type="institution" xml:id="struct-423110" status="INCOMING"> <orgName>Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><hal:affiliation type="institution" xml:id="struct-420494" status="INCOMING"> <orgName>Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><hal:affiliation type="institution" xml:id="struct-420496" status="INCOMING"> <orgName>Brown Foundation Institute of Molecular Medicine, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA.</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </hal:affiliation></affiliation></author></analytic><idno type="DOI">10.1161/CIRCGENETICS.114.000858</idno><series><title level="j">Circulation: Cardiovascular Genetics</title><idno type="ISSN">1942-325X</idno><imprint><date type="datePub">2015-03-31</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>cerebral small vessel diseases</term><term>cerebrovascular disorders</term><term>genome-wide association study</term><term>hypertension</term><term>leukoencephalopathies</term><term>polymorphisms</term><term>single nucleotide</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.</div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.</title> <author role="aut"> <persName> <forename type="first">Benjamin F J</forename> <surname>Verhaaren</surname> </persName> <idno type="halauthorid">1170696</idno> <affiliation ref="#struct-420509"></affiliation> <affiliation ref="#struct-420494"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Stéphanie</forename> <surname>Debette</surname> </persName> <idno type="halauthorid">300623</idno> <affiliation ref="#struct-431520"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Joshua C</forename> <surname>Bis</surname> </persName> <idno type="halauthorid">1170686</idno> <affiliation ref="#struct-420488"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jennifer A</forename> <surname>Smith</surname> </persName> <idno type="halauthorid">1214027</idno> <affiliation ref="#struct-432651"></affiliation> </author> <author role="aut"> <persName> <forename type="first">M Kamran</forename> <surname>Ikram</surname> </persName> <idno type="halauthorid">1214028</idno> <affiliation ref="#struct-420494"></affiliation> <affiliation ref="#struct-420506"></affiliation> <affiliation ref="#struct-420523"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Hieab H</forename> <surname>Adams</surname> </persName> <idno type="halauthorid">1214029</idno> <affiliation ref="#struct-21646"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ashley H</forename> <surname>Beecham</surname> </persName> <idno type="halauthorid">1214030</idno> <affiliation ref="#struct-233324"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Kumar B</forename> <surname>Rajan</surname> </persName> <idno type="halauthorid">1214031</idno> <affiliation ref="#struct-432652"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Lorna M</forename> <surname>Lopez</surname> </persName> <idno type="halauthorid">1212032</idno> <affiliation ref="#struct-431805"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sandra</forename> <surname>Barral</surname> </persName> <idno type="halauthorid">1214032</idno> <affiliation ref="#struct-61277"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Mark A</forename> <surname>van Buchem</surname> </persName> <idno type="halauthorid">1170708</idno> <affiliation ref="#struct-420519"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jeroen</forename> <surname>van der Grond</surname> </persName> <idno type="halauthorid">1214033</idno> <affiliation ref="#struct-432653"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Albert V</forename> <surname>Smith</surname> </persName> <idno type="halauthorid">644762</idno> <affiliation ref="#struct-3747"></affiliation> <affiliation ref="#struct-302627"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Katrin</forename> <surname>Hegenscheid</surname> </persName> <idno type="halauthorid">1212063</idno> <affiliation ref="#struct-431819"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Neelum T</forename> <surname>Aggarwal</surname> </persName> <idno type="halauthorid">1214034</idno> <affiliation ref="#struct-432652"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Mariza</forename> <surname>De Andrade</surname> </persName> <idno type="halauthorid">214235</idno> <affiliation ref="#struct-485956"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Elizabeth J</forename> <surname>Atkinson</surname> </persName> <idno type="halauthorid">1214035</idno> <affiliation ref="#struct-328644"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marian</forename> <surname>Beekman</surname> </persName> <idno type="halauthorid">535663</idno> <affiliation ref="#struct-1126"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexa S</forename> <surname>Beiser</surname> </persName> <idno type="halauthorid">1214036</idno> <affiliation ref="#struct-423110"></affiliation> <affiliation ref="#struct-420206"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Susan H</forename> <surname>Blanton</surname> </persName> <idno type="halauthorid">667766</idno> <affiliation ref="#struct-176444"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Eric</forename> <surname>Boerwinkle</surname> </persName> <idno type="halauthorid">978014</idno> <affiliation ref="#struct-420196"></affiliation> <affiliation ref="#struct-420197"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Adam M</forename> <surname>Brickman</surname> </persName> <idno type="halauthorid">1214037</idno> <affiliation ref="#struct-101530"></affiliation> </author> <author role="aut"> <persName> <forename type="first">R Nick</forename> <surname>Bryan</surname> </persName> <idno type="halauthorid">1214038</idno> <affiliation ref="#struct-432654"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ganesh</forename> <surname>Chauhan</surname> </persName> <idno type="halauthorid">1211222</idno> <affiliation ref="#struct-431530"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christopher P L H</forename> <surname>Chen</surname> </persName> <idno type="halauthorid">1214039</idno> <affiliation ref="#struct-1194"></affiliation> </author> <author 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ref="#struct-420531"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Hans J</forename> <surname>Grabe</surname> </persName> <idno type="halauthorid">1212136</idno> <affiliation ref="#struct-268175"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sudha S</forename> <surname>Seshadri</surname> </persName> <idno type="halauthorid">1214073</idno> <affiliation ref="#struct-423110"></affiliation> </author> <author role="aut"> <persName> <forename type="first">M Arfan</forename> <surname>Ikram</surname> </persName> <idno type="halauthorid">1170740</idno> <affiliation ref="#struct-420494"></affiliation> <affiliation ref="#struct-420506"></affiliation> <affiliation ref="#struct-420523"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Myriam</forename> <surname>Fornage</surname> </persName> <idno type="halauthorid">1170689</idno> <affiliation ref="#struct-420496"></affiliation> <affiliation ref="#struct-420497"></affiliation> </author> <editor role="depositor"> <persName> <forename>GIN</forename> <surname>Hal</surname> </persName> <email type="md5">4bf5fbd73ce1f0ea01c4771f70a45ea9</email> <email type="domain">gmail.com</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2015-09-14 11:52:01</date> <date type="whenModified">2017-10-26 16:34:02</date> <date type="whenReleased">2015-09-16 16:46:47</date> <date type="whenProduced">2015-03-31</date> <date type="whenEndEmbargoed">2015-09-16</date> <ref type="file" target="https://hal.archives-ouvertes.fr/hal-01198723/document"> <date notBefore="2015-09-16"></date> </ref> <ref type="file" subtype="author" n="1" target="https://hal.archives-ouvertes.fr/hal-01198723/file/Verhaaren_CircCardiovascGenet_15.pdf"> <date notBefore="2015-09-16"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="314613"> <persName> <forename>GIN</forename> <surname>Hal</surname> </persName> <email type="md5">4bf5fbd73ce1f0ea01c4771f70a45ea9</email> <email type="domain">gmail.com</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">hal-01198723</idno> <idno type="halUri">https://hal.archives-ouvertes.fr/hal-01198723</idno> <idno type="halBibtex">verhaaren:hal-01198723</idno> <idno type="halRefHtml">Circulation: Cardiovascular Genetics, American Heart Association, 2015, 8 (2), pp.398-409. 〈10.1161/CIRCGENETICS.114.000858〉</idno> <idno type="halRef">Circulation: Cardiovascular Genetics, American Heart Association, 2015, 8 (2), pp.398-409. 〈10.1161/CIRCGENETICS.114.000858〉</idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> <idno type="stamp" n="UNIV-STRASBG1">Université Louis Pasteur - Strasbourg I</idno> <idno type="stamp" n="UNIV-STRASBG">Université de Strasbourg</idno> <idno type="stamp" n="SATIE">Systèmes et Applications des Technologies de l'Information et de l'Energie</idno> <idno type="stamp" n="UNIV-AMU">Aix Marseille Université</idno> <idno type="stamp" n="CEA">CEA - Commissariat à l'énergie atomique</idno> <idno type="stamp" n="UNIV-TLSE3">Université Paul Sabatier - Toulouse III</idno> <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno> <idno type="stamp" n="UGA">HAL Grenoble Alpes</idno> <idno type="stamp" n="ENS-CACHAN">Ecole Normale Supérieure de Cachan</idno> <idno type="stamp" n="GIN">Groupe d'imagerie neurofonctionnelle</idno> <idno type="stamp" n="UNIV-CERGY">Université de Cergy Pontoise</idno> <idno type="stamp" n="CNAM">Conservatoire National des Arts et Métiers</idno> <idno type="stamp" n="IFSTTAR">Ifsttar</idno> <idno type="stamp" n="UNIV-PSUD">Université Paris Sud - Paris XI</idno> <idno type="stamp" n="UNIV-PSUD-SACLAY" p="UNIV-PARIS-SACLAY">Université Paris Sud pour Paris Saclay</idno> <idno type="stamp" n="ENS-CACHAN-SACLAY" p="UNIV-PARIS-SACLAY">ENS-CACHAN-SACLAY</idno> <idno type="stamp" n="UNIV-PARIS-SACLAY">Université Paris-Saclay</idno> <idno type="stamp" n="UNIV-PARIS7">Université Denis Diderot - Paris VII</idno> <idno type="stamp" n="INSU">INSU - Institut National des Sciences de l'Univers</idno> <idno type="stamp" n="USPC">Université Sorbonne Paris Cité</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.</title> <author role="aut"> <persName> <forename type="first">Benjamin F J</forename> <surname>Verhaaren</surname> </persName> <idno type="halauthorid">1170696</idno> <affiliation ref="#struct-420509"></affiliation> <affiliation ref="#struct-420494"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Stéphanie</forename> <surname>Debette</surname> </persName> <idno type="halauthorid">300623</idno> <affiliation ref="#struct-431520"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Joshua C</forename> <surname>Bis</surname> </persName> <idno type="halauthorid">1170686</idno> <affiliation ref="#struct-420488"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jennifer A</forename> <surname>Smith</surname> </persName> <idno type="halauthorid">1214027</idno> <affiliation ref="#struct-432651"></affiliation> </author> <author role="aut"> <persName> <forename type="first">M Kamran</forename> <surname>Ikram</surname> </persName> <idno type="halauthorid">1214028</idno> <affiliation ref="#struct-420494"></affiliation> <affiliation ref="#struct-420506"></affiliation> <affiliation ref="#struct-420523"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Hieab H</forename> <surname>Adams</surname> </persName> <idno type="halauthorid">1214029</idno> <affiliation ref="#struct-21646"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ashley H</forename> <surname>Beecham</surname> </persName> <idno type="halauthorid">1214030</idno> <affiliation ref="#struct-233324"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Kumar B</forename> <surname>Rajan</surname> </persName> <idno type="halauthorid">1214031</idno> <affiliation ref="#struct-432652"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Lorna M</forename> <surname>Lopez</surname> </persName> <idno type="halauthorid">1212032</idno> <affiliation ref="#struct-431805"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sandra</forename> <surname>Barral</surname> </persName> <idno type="halauthorid">1214032</idno> <affiliation ref="#struct-61277"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Mark A</forename> <surname>van Buchem</surname> </persName> <idno type="halauthorid">1170708</idno> <affiliation ref="#struct-420519"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jeroen</forename> <surname>van der Grond</surname> </persName> <idno type="halauthorid">1214033</idno> <affiliation ref="#struct-432653"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Albert V</forename> <surname>Smith</surname> </persName> <idno type="halauthorid">644762</idno> <affiliation ref="#struct-3747"></affiliation> <affiliation ref="#struct-302627"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Katrin</forename> <surname>Hegenscheid</surname> </persName> <idno type="halauthorid">1212063</idno> <affiliation ref="#struct-431819"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Neelum T</forename> <surname>Aggarwal</surname> </persName> <idno type="halauthorid">1214034</idno> <affiliation ref="#struct-432652"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Mariza</forename> <surname>De Andrade</surname> </persName> <idno type="halauthorid">214235</idno> <affiliation ref="#struct-485956"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Elizabeth J</forename> <surname>Atkinson</surname> </persName> <idno type="halauthorid">1214035</idno> <affiliation ref="#struct-328644"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marian</forename> <surname>Beekman</surname> </persName> <idno type="halauthorid">535663</idno> <affiliation ref="#struct-1126"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexa S</forename> <surname>Beiser</surname> </persName> <idno type="halauthorid">1214036</idno> <affiliation ref="#struct-423110"></affiliation> <affiliation ref="#struct-420206"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Susan H</forename> <surname>Blanton</surname> </persName> <idno type="halauthorid">667766</idno> <affiliation ref="#struct-176444"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Eric</forename> <surname>Boerwinkle</surname> </persName> <idno type="halauthorid">978014</idno> <affiliation ref="#struct-420196"></affiliation> <affiliation ref="#struct-420197"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Adam M</forename> <surname>Brickman</surname> </persName> <idno type="halauthorid">1214037</idno> <affiliation ref="#struct-101530"></affiliation> </author> <author role="aut"> <persName> <forename type="first">R Nick</forename> <surname>Bryan</surname> </persName> <idno type="halauthorid">1214038</idno> <affiliation ref="#struct-432654"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ganesh</forename> <surname>Chauhan</surname> </persName> <idno type="halauthorid">1211222</idno> <affiliation ref="#struct-431530"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christopher P L H</forename> <surname>Chen</surname> </persName> <idno type="halauthorid">1214039</idno> <affiliation ref="#struct-1194"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Vincent</forename> <surname>Chouraki</surname> </persName> <idno type="idhal" notation="string">vincent-chouraki</idno> <idno type="idhal" notation="numeric">15351</idno> <idno type="halauthorid">812965</idno> <idno type="ORCID">http://orcid.org/0000-0002-4698-1794</idno> <affiliation ref="#struct-164505"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Anton J M</forename> <surname>de Craen</surname> </persName> <idno type="halauthorid">1214040</idno> <affiliation ref="#struct-138291"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Fabrice</forename> <surname>Crivello</surname> </persName> <idno type="halauthorid">212699</idno> <affiliation ref="#struct-247162"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ian J</forename> <surname>Deary</surname> </persName> <idno type="halauthorid">564407</idno> <affiliation ref="#struct-156485"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Joris</forename> <surname>Deelen</surname> </persName> <idno type="halauthorid">1145729</idno> <affiliation ref="#struct-331670"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philip L</forename> <surname>De Jager</surname> </persName> <idno type="halauthorid">1170727</idno> <affiliation ref="#struct-420541"></affiliation> <affiliation ref="#struct-420501"></affiliation> <affiliation ref="#struct-420500"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Carole</forename> <surname>Dufouil</surname> </persName> <idno 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</author> <author role="aut"> <persName> <forename type="first">Aad</forename> <surname>van der Lugt</surname> </persName> <idno type="halauthorid">1170733</idno> <affiliation ref="#struct-420493"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Oliver O</forename> <surname>Martinez</surname> </persName> <idno type="halauthorid">1214054</idno> <affiliation ref="#struct-583"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Richard</forename> <surname>Mayeux</surname> </persName> <idno type="halauthorid">714306</idno> <affiliation ref="#struct-189902"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bernard</forename> <surname>Mazoyer</surname> </persName> <idno type="halauthorid">134875</idno> <affiliation ref="#struct-247162"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Mike</forename> <surname>Nalls</surname> </persName> <idno type="halauthorid">1214055</idno> <affiliation ref="#struct-420532"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Matthias</forename> <surname>Nauck</surname> </persName> <idno type="halauthorid">209245</idno> <affiliation ref="#struct-167197"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Wiro J</forename> <surname>Niessen</surname> </persName> <idno type="halauthorid">1170713</idno> <affiliation ref="#struct-420493"></affiliation> <affiliation ref="#struct-420494"></affiliation> <affiliation ref="#struct-420522"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ben A</forename> <surname>Oostra</surname> </persName> <idno type="halauthorid">1145906</idno> <affiliation ref="#struct-420526"></affiliation> <affiliation ref="#struct-420505"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bruce M</forename> <surname>Psaty</surname> </persName> <idno type="halauthorid">698381</idno> <affiliation 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role="aut"> <persName> <forename type="first">J Wouter</forename> <surname>Jukema</surname> </persName> <idno type="halauthorid">1214070</idno> <affiliation ref="#struct-307012"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Ralph L</forename> <surname>Sacco</surname> </persName> <idno type="halauthorid">645400</idno> <affiliation ref="#struct-432668"></affiliation> <affiliation ref="#struct-432669"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sharon L R</forename> <surname>Kardia</surname> </persName> <idno type="halauthorid">1214071</idno> <affiliation ref="#struct-432651"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philippe</forename> <surname>Amouyel</surname> </persName> <idno type="halauthorid">108293</idno> <affiliation ref="#struct-423244"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Thomas H</forename> <surname>Mosley</surname> </persName> <idno type="halauthorid">1170737</idno> <affiliation ref="#struct-420520"></affiliation> <affiliation ref="#struct-420547"></affiliation> </author> <author role="aut"> <persName> <forename type="first">W T</forename> <surname>Longstreth</surname> </persName> <idno type="halauthorid">1170734</idno> <affiliation ref="#struct-420543"></affiliation> <affiliation ref="#struct-420544"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Charles C</forename> <surname>DeCarli</surname> </persName> <idno type="halauthorid">1214072</idno> <affiliation ref="#struct-423113"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Cornelia M</forename> <surname>van Duijn</surname> </persName> <idno type="halauthorid">1145923</idno> <affiliation ref="#struct-420505"></affiliation> <affiliation ref="#struct-420523"></affiliation> <affiliation ref="#struct-420546"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Reinhold</forename> <surname>Schmidt</surname> </persName> <idno type="halauthorid">1170738</idno> <affiliation ref="#struct-196396"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Lenore J</forename> <surname>Launer</surname> </persName> <idno type="halauthorid">1170739</idno> <affiliation ref="#struct-420531"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Hans J</forename> <surname>Grabe</surname> </persName> <idno type="halauthorid">1212136</idno> <affiliation ref="#struct-268175"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Sudha S</forename> <surname>Seshadri</surname> </persName> <idno type="halauthorid">1214073</idno> <affiliation ref="#struct-423110"></affiliation> </author> <author role="aut"> <persName> <forename type="first">M Arfan</forename> <surname>Ikram</surname> </persName> <idno type="halauthorid">1170740</idno> <affiliation ref="#struct-420494"></affiliation> <affiliation ref="#struct-420506"></affiliation> <affiliation ref="#struct-420523"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Myriam</forename> <surname>Fornage</surname> </persName> <idno type="halauthorid">1170689</idno> <affiliation ref="#struct-420496"></affiliation> <affiliation ref="#struct-420497"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">87646</idno> <idno type="issn">1942-325X</idno> <idno type="eissn">1942-3268</idno> <title level="j">Circulation: Cardiovascular Genetics</title> <imprint> <publisher>American Heart Association</publisher> <biblScope unit="volume">8</biblScope> <biblScope unit="issue">2</biblScope> <biblScope unit="pp">398-409</biblScope> <date type="datePub">2015-03-31</date> </imprint> </monogr> <idno type="doi">10.1161/CIRCGENETICS.114.000858</idno> <idno type="pubmedcentral">PMC4427240</idno> <idno type="pubmed">25663218</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">single nucleotide</term> <term xml:lang="en">hypertension</term> <term xml:lang="en">genome-wide association study</term> <term xml:lang="en">cerebrovascular disorders</term> <term xml:lang="en">cerebral small vessel diseases</term> <term xml:lang="en">leukoencephalopathies</term> <term xml:lang="en">polymorphisms</term> </keywords> <classCode scheme="halDomain" n="scco.neur">Cognitive science/Neuroscience</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en">The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.</abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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